MDMA Enhances Emotional Empathy and Prosocial Behavior

Cédric M. Hysek; Yasmin Schmid; Linda D. Simmler; Gregor Domes; Markus Heinrichs; Christoph Eisenegger; Katrin H. Preller; Boris B. Quednow; Matthias E. Liechti

Disclosures

Soc Cogn Affect Neurosci. 2014;9(11):1645-1652. 

In This Article

Results

Mean ± s.e.m. values and detailed statistics for all outcomes are shown in Supplementary Table S1 http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1.

Subjective Effects

Significant MDMA treatment effects were found on VAS scores for 'happy' (F 1,31 = 120.59, P < 0.001), 'open' (F 1,31 = 80.77, P < 0.001) and 'close to others' (F 1,31 = 67.52, P < 0.001; Figure 1). MDMA also increased AMRS scores for activity (F 1,31 = 24.48, P < 0.001), inactivity (F 1,31 = 7.72, P = 0.009), extroversion (F 1,31 = 40.58, P < 0.001), introversion (F 1,31 = 10.05, P = 0.003), well-being (F 1,31 = 37.00, P < 0.001), emotional excitation (F 1,31 = 28.46, P < 0.001) and dreaminess (F 1,31 = 25.48, P < 0.001) but not for anxiety (Supplementary Figure S1 http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). A significant sex × treatment interaction was found for 'happy' ratings (F 1,31 = 10.49, P = 0.003), but the post hoc tests showed no significant differences between men and women in 'happy' ratings after MDMA administration. No other sex × treatment interactions were found.

Figure 1.

Subjective effects of MDMA measured using VASs. The data are expressed as mean ± s.e.m. score changes from predrug baseline in 32 subjects. ***P < 0.001, significant differences (E max) from placebo in women/men.

Empathy

MDMA significantly increased explicit and implicit emotional empathy ratings for all stimuli (F 1,31 = 6.05, P = 0.019 and F 1,31 = 4.29, P = 0.047, respectively) (Figure 2A and B). For both explicit and implicit empathy, the MDMA-induced increase was significant for positive valence stimuli (F 1,31 = 8.60, P = 0.006 and F 1,31 = 5.02, P = 0.032, respectively) but not negative valence stimuli (Supplementary Figure S2A–D http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). MDMA influenced emotional empathy differently in male and female subjects as evidenced by a significant treatment × sex interaction for implicit emotional empathy (F 1,31 = 4.68, P = 0.039) and a similar trend effect for explicit emotional empathy (F 1,31 = 3.03, P = 0.092). The post hoc tests showed that MDMA increased explicit and implicit emotional empathy ratings only in men (P = 0.025 and P = 0.022, respectively) and not in women (Figure 2A and B). Men tended to score non-significantly lower on both measures of emotional empathy compared with women after placebo administration. MDMA increased empathy ratings in men to the levels of empathy in women after placebo administration. No effect of treatment was found on cognitive empathy scores (Figure 2C). Trait empathy in the IRI did not moderate the state empathy response to MDMA in the MET. As expected and validating the tasks, IRI trait empathy ratings of fantasy and empathic concern were associated with explicit empathy scores in the MET (R p = 0.60, P < 0.05 and R p = 0.47, P < 0.05, respectively; n = 32), and IRI trait empathy ratings of personal distress were associated with implicit emotional empathy ratings in the MET (R p = 0.63, P < 0.01; n = 32) after placebo administration.

Figure 2.

Effect of MDMA on (A) explicit and (B) implicit emotional empathy and (C) cognitive empathy in the MET. MDMA significantly increased emotional empathy in all subjects due to increases in men but not in women. The data are expressed as mean ± s.e.m. in 32 subjects. *P < 0.05, significant difference from placebo.

Social Value Orientation

MDMA increased prosociality. A significant MDMA treatment effect was found on the SVO angle (F 1,31 = 4.42, P = 0.044; Figure 3A), with a significant treatment × sex interaction (F 1,31 = 5.52, P = 0.026). The post hoc tests showed that MDMA significantly increased prosocial behavior in men (P = 0.008) but not women. In men, prosocial behavior increased after MDMA administration to the levels of placebo-treated women (Figure 3A). Moreover, MDMA tended to reduce the inequality-aversion index (F 1,20 = 3.39, P = 0.079) in subjects with a prosocial orientation, indicating that MDMA promoted the shift from joint gain maximization to inequality aversion (Figure 3B).

Figure 3.

Effect of MDMA on prosociality and inequality-aversion in the SVO test. (A) MDMA had prosocial effects in men, resulting in levels of prosociality equal to those of placebo-treated women. (B) MDMA tended to reduce the inequality-aversion index (P = 0.079), consistent with an increased preference for fairness. The data are expressed as mean ± s.e.m. *P < 0.05, significant difference from placebo.

Facial Emotion Recognition

MDMA impaired the accuracy of emotion recognition compared with placebo (F 1,31 = 28.63, P < 0.001) when all of the stimuli were analyzed together, regardless of valence (Supplementary Figure S3A http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). MDMA differently affected emotion recognition in male and female subjects (F 1,31 = 6.04, P = 0.020). Women performed significantly worse after MDMA treatment compared with placebo treatment (P < 0.001), whereas no significant effect of MDMA was found in men (Supplementary Figure S3A http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). Valence-specific analyses of recognition accuracy showed that MDMA significantly impaired the correct recognition of fearful (F 1,31 = 14.90, P < 0.001), angry (F 1,31 = 18.60, P < 0.001), disgusted (F 1,31 = 5.81, P = 0.022) and surprised (F 1,31 = 9.79, P = 0.004) faces compared with placebo (Supplementary Figure S3D, E, G and H http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). In contrast, MDMA did not alter the correct identification of happy (F 1,31 = 0.27, P = 0.607) faces compared with placebo (Supplementary Figure S3C http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). MDMA affected recognition accuracy for fearful and sad faces differently in male and female subjects (F 1,31 = 6.61, P = 0.015 and F 1,31 = 9.42, P = 0.005, respectively). Significant impairments in the recognition accuracy for fearful (P < 0.001), angry (P = 0.007) and sad (P = 0.010) faces after MDMA treatment compared with placebo were found only in women (Supplementary Figure S3E and F http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). Fear recognition accuracy inversely correlated with the C max and AUC0 6 h of MDMA in women (R p = −0.62, P = 0.014 and R p = −0.66, P = 0.006, respectively; n = 16).

Consistent with labeling errors for fearful faces, MDMA increased the detection threshold for fearful faces compared with placebo (F 1,31 = 4.92, P < 0.032). MDMA did not alter the detection threshold for any other valence or all of the emotions together (Supplementary Figure S3B http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). Accuracy in the MET significantly correlated with overall emotion recognition accuracy in the FERT (R p = 0.42, P = 0.018; n = 32) after placebo treatment, thus cross-validating both tasks. No correlations were found between the effects of MDMA on emotion recognition and the endocrine effects of MDMA.

Endocrine Effects and Pharmacokinetics of MDMA

MDMA significantly increased the plasma levels of oxytocin (F 1,31 = 19.84, P < 0.001), cortisol (F 1,31 = 98.70, P < 0.001) and prolactin (F 1,31 = 127.81, P < 0.001) compared with placebo (Figure 4A, C, and D). In contrast, MDMA did not alter the plasma concentrations of copeptin (Figure 4B) or testosterone (Supplementary Table S1 http://scan.oxfordjournals.org/content/9/11/1645/suppl/DC1). No correlations were found between the neuroendocrine and empathogenic or prosocial effects of MDMA.

Figure 4.

(A–D) Endocrine effects of MDMA and (E) plasma concentration-time curve of MDMA. MDMA increased the plasma concentrations of (A) oxytocin, (C) cortisol and (D) prolactin but not (B) copeptin. The data are expressed as mean ± s.e.m. of differences from baseline in 32 subjects. *P < 0.05, **P < 0.01, ***P < 0.001, significant difference (change in C max) from placebo.

Both the maximum concentration (C max) and area under the plasma concentration-time curve (AUC0 6 h) were higher in women compared with men (F 1,15 = 35.73, P < 0.001 and F 1,15 = 20.77, P < 0.001, respectively) (Figure 4E). The mean C max values of MDMA were 209 ± 6.4 ng/ml (mean ± s.e.m.) in men and 269.9 ± 9.3 ng/ml (mean ± s.e.m.) in women. Mean AUC0 6 h values were 926.8 ± 29.3 ng/ml h (mean ± s.e.m.) in men and 1146.5 ± 37.9 ng/ml h (mean ± s.e.m.) in women. The relative doses of MDMA were 1.68 ± 0.14 mg/kg body weight (mean ± s.d.) in men and 2.09 ± 0.29 mg/kg body weight (mean ± s.d.) in women. Higher plasma exposure to MDMA was significantly associated with deficits in the recognition of fearful faces in women as described above. No other correlations were found between plasma exposure to MDMA and the pharmacodynamic effects of MDMA. The time to maximum concentration (T max) was reached after a mean time of 2.44 ± 0.14 h (mean ± s.e.m.) after MDMA administration. Mean T max values were 2.10 ± 0.20 h (mean ± s.e.m.) and 2.75 ± 0.17 h (mean ± s.e.m.) in men and women, respectively. The pharmacokinetic data were consistent with previous studies (Hysek et al., 2011; Hysek and Liechti, 2012).

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